The Potential Role of Thyroid Hormone Therapy in Neural Progenitor Cell Differentiation and Its Impact on Neurodevelopmental Disorders

<p dir="ltr">Thyroid hormone (T3) plays a vital role in brain development and its dysregulation can impact behavior, nervous system function, and cognitive development. Large case-cohort studies have associated abnormal maternal T3 during early pregnancy to epilepsy, autism, and atte...

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Main Author: Salam Salloum-Asfar (656363) (author)
Other Authors: Kyung Chul Shin (13913556) (author), Rowaida Z. Taha (8854754) (author), Shahryar Khattak (291870) (author), Yongsoo Park (761850) (author), Sara A. Abdulla (13902015) (author)
Published: 2023
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author Salam Salloum-Asfar (656363)
author2 Kyung Chul Shin (13913556)
Rowaida Z. Taha (8854754)
Shahryar Khattak (291870)
Yongsoo Park (761850)
Sara A. Abdulla (13902015)
author2_role author
author
author
author
author
author_facet Salam Salloum-Asfar (656363)
Kyung Chul Shin (13913556)
Rowaida Z. Taha (8854754)
Shahryar Khattak (291870)
Yongsoo Park (761850)
Sara A. Abdulla (13902015)
author_role author
dc.creator.none.fl_str_mv Salam Salloum-Asfar (656363)
Kyung Chul Shin (13913556)
Rowaida Z. Taha (8854754)
Shahryar Khattak (291870)
Yongsoo Park (761850)
Sara A. Abdulla (13902015)
dc.date.none.fl_str_mv 2023-11-22T03:00:00Z
dc.identifier.none.fl_str_mv 10.1007/s12035-023-03751-8
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/The_Potential_Role_of_Thyroid_Hormone_Therapy_in_Neural_Progenitor_Cell_Differentiation_and_Its_Impact_on_Neurodevelopmental_Disorders/24998291
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Biochemistry and cell biology
Biomedical and clinical sciences
Neurosciences
Thyroid hormone
Neuronal diferentiation
eurodevelopmental disorders
Cortical diferentiation
ADHD
dc.title.none.fl_str_mv The Potential Role of Thyroid Hormone Therapy in Neural Progenitor Cell Differentiation and Its Impact on Neurodevelopmental Disorders
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">Thyroid hormone (T3) plays a vital role in brain development and its dysregulation can impact behavior, nervous system function, and cognitive development. Large case-cohort studies have associated abnormal maternal T3 during early pregnancy to epilepsy, autism, and attention deficit hyperactivity disorder (ADHD) in children. Recent experimental findings have also shown T3’s influence on the fate of neural precursor cells and raise the question of its convergence with embryonic neural progenitors. Our objective was to investigate how T3 treatment affects neuronal development and functionality at the cellular level. In vitro experiments using neural precursor cells (NPCs) measured cell growth and numbers after exposure to varying T3 concentrations. Time points included week 0 (W0) representing NPCs treated with 100 nM T3 for 5 days, and differentiated cortical neurons assessed at weeks 3 (W3), 6 (W6), and 8 (W8). Techniques such as single-cell calcium imaging and whole-cell patch clamp were utilized to evaluate neuronal activity and function. IHC staining detected mature neuron markers, and RNA sequencing enabled molecular profiling. W6 and W8 neurons exhibited higher action potential frequencies, with W6 showing increased peak amplitudes and shortened inter-spike intervals by 50%, indicating enhanced activity. Transcriptomic analysis revealed that W6 T3-treated neurons formed a distinct cluster, suggesting accelerated maturation. Comparison with the whole transcriptome further unveiled a correlation between W6 neurons treated with T3 and neuronal regulatory elements associated with autism and ADHD. These findings provide insights into T3’s impact on neuronal development and potential mechanisms of T3 dysregulation and neurodevelopmental disorders.</p><h2>Other Information</h2><p dir="ltr">Published in: Molecular Neurobiology<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s12035-023-03751-8" target="_blank">https://dx.doi.org/10.1007/s12035-023-03751-8</a></p>
eu_rights_str_mv openAccess
id Manara2_1bac71d3de82f5f935b0a65782983892
identifier_str_mv 10.1007/s12035-023-03751-8
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/24998291
publishDate 2023
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rights_invalid_str_mv CC BY 4.0
spelling The Potential Role of Thyroid Hormone Therapy in Neural Progenitor Cell Differentiation and Its Impact on Neurodevelopmental DisordersSalam Salloum-Asfar (656363)Kyung Chul Shin (13913556)Rowaida Z. Taha (8854754)Shahryar Khattak (291870)Yongsoo Park (761850)Sara A. Abdulla (13902015)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesNeurosciencesThyroid hormoneNeuronal diferentiationeurodevelopmental disordersCortical diferentiationADHD<p dir="ltr">Thyroid hormone (T3) plays a vital role in brain development and its dysregulation can impact behavior, nervous system function, and cognitive development. Large case-cohort studies have associated abnormal maternal T3 during early pregnancy to epilepsy, autism, and attention deficit hyperactivity disorder (ADHD) in children. Recent experimental findings have also shown T3’s influence on the fate of neural precursor cells and raise the question of its convergence with embryonic neural progenitors. Our objective was to investigate how T3 treatment affects neuronal development and functionality at the cellular level. In vitro experiments using neural precursor cells (NPCs) measured cell growth and numbers after exposure to varying T3 concentrations. Time points included week 0 (W0) representing NPCs treated with 100 nM T3 for 5 days, and differentiated cortical neurons assessed at weeks 3 (W3), 6 (W6), and 8 (W8). Techniques such as single-cell calcium imaging and whole-cell patch clamp were utilized to evaluate neuronal activity and function. IHC staining detected mature neuron markers, and RNA sequencing enabled molecular profiling. W6 and W8 neurons exhibited higher action potential frequencies, with W6 showing increased peak amplitudes and shortened inter-spike intervals by 50%, indicating enhanced activity. Transcriptomic analysis revealed that W6 T3-treated neurons formed a distinct cluster, suggesting accelerated maturation. Comparison with the whole transcriptome further unveiled a correlation between W6 neurons treated with T3 and neuronal regulatory elements associated with autism and ADHD. These findings provide insights into T3’s impact on neuronal development and potential mechanisms of T3 dysregulation and neurodevelopmental disorders.</p><h2>Other Information</h2><p dir="ltr">Published in: Molecular Neurobiology<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s12035-023-03751-8" target="_blank">https://dx.doi.org/10.1007/s12035-023-03751-8</a></p>2023-11-22T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s12035-023-03751-8https://figshare.com/articles/journal_contribution/The_Potential_Role_of_Thyroid_Hormone_Therapy_in_Neural_Progenitor_Cell_Differentiation_and_Its_Impact_on_Neurodevelopmental_Disorders/24998291CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/249982912023-11-22T03:00:00Z
spellingShingle The Potential Role of Thyroid Hormone Therapy in Neural Progenitor Cell Differentiation and Its Impact on Neurodevelopmental Disorders
Salam Salloum-Asfar (656363)
Biological sciences
Biochemistry and cell biology
Biomedical and clinical sciences
Neurosciences
Thyroid hormone
Neuronal diferentiation
eurodevelopmental disorders
Cortical diferentiation
ADHD
status_str publishedVersion
title The Potential Role of Thyroid Hormone Therapy in Neural Progenitor Cell Differentiation and Its Impact on Neurodevelopmental Disorders
title_full The Potential Role of Thyroid Hormone Therapy in Neural Progenitor Cell Differentiation and Its Impact on Neurodevelopmental Disorders
title_fullStr The Potential Role of Thyroid Hormone Therapy in Neural Progenitor Cell Differentiation and Its Impact on Neurodevelopmental Disorders
title_full_unstemmed The Potential Role of Thyroid Hormone Therapy in Neural Progenitor Cell Differentiation and Its Impact on Neurodevelopmental Disorders
title_short The Potential Role of Thyroid Hormone Therapy in Neural Progenitor Cell Differentiation and Its Impact on Neurodevelopmental Disorders
title_sort The Potential Role of Thyroid Hormone Therapy in Neural Progenitor Cell Differentiation and Its Impact on Neurodevelopmental Disorders
topic Biological sciences
Biochemistry and cell biology
Biomedical and clinical sciences
Neurosciences
Thyroid hormone
Neuronal diferentiation
eurodevelopmental disorders
Cortical diferentiation
ADHD